DESCRIPTION (the applicant?s description verbatim): Vitamin A (retinol) has long been known to be essential for normal development, and vitamin A deficiency (VAD) can result in developmental malformations of many different tissues including limb, palate, skull, kidney and heart. The long term objective of the proposal is an increased understanding of the role retinol binding protein (RBP) plays in the delivery of Vitamin A to embryonic tissues. The role of RBP in the delivery of vitamin A in the adult circulation is well documented, but its function in the early embryo is poorly understood. The specific aims of this proposal are to examine embryogenesis in RBP knockout mice, and specifically study the effect of RBP deletion on cardiogenesis. This will be achieved by examining embryogenesis in mice with a targeted knockout of the RBP gene. In addition, the creloxP system will be used to produce a conditional knockout of RBP, which will delete RBP from the heart only. The final aim will be to use knockout mice and wild type mice to study VAD over specific time windows, in order to determine the stage of heart development at which delivery of vitamin A is critical. Overall this project will provide a better understanding of the role and delivery of vitamin A during early cardiogenesis.